Sionna Therapeutics (Nasdaq: SION) reported that its Phase 2a proof-of-concept trial of SION-719, tested as an add-on to the cystic fibrosis standard of care treatment Trikafta, failed to meet its key activity endpoint of sweat chloride reduction.

The PreciSION CF trial, which enrolled 15 adult cystic fibrosis patients homozygous for F508del, showed a mean placebo-adjusted sweat chloride change of -1.0 mmol/L (p=0.7). Sionna said it will not advance SION-719 as an add-on to standard of care.

The company noted potential confounders in the trial, including higher-than-anticipated variability in individual sweat chloride levels and differences in Trikafta exposure levels between the SION-719 and placebo periods. Sionna said it is evaluating the impact of these factors on interpreting the trial data.

SION-719 was reported as generally well tolerated over the 14-day treatment period, with most adverse events rated mild to moderate, no serious adverse events, and no meaningful trends in liver function abnormalities.

In a separate Phase 1 healthy volunteer trial involving 120 participants, Sionna's SION-451 in dual combinations with either SION-2222 or SION-109 met its safety, tolerability, and pharmacokinetic objectives. The company identified SION-451 combined with SION-2222 as the preferred dual combination based on the totality of the data. Sionna said it is evaluating next steps for the SION-451 program, taking into account the PreciSION CF trial results.

"We are disappointed in the unexpected results from the Phase 2a trial. We are further evaluating the data to decide on next steps for the SION-451 dual combination," said Mike Cloonan, President and Chief Executive Officer of Sionna.

Sionna ended the second quarter with approximately $268.3 million in cash, cash equivalents, and marketable securities. The company stated it intends to take actions to preserve capital while evaluating next steps.